Abstract
Liver diseases, including viral hepatitis, liver cirrhosis, and liver cancer, mostly remain silent until the late stages and pose a continuing threat to millions of people worldwide. Liver transplantation is the most appropriate solution in the case of liver failure, but it is associated with hepatic ischemia and reperfusion (I/R) injury which severely reduces the prognosis of the patients. In order to ameliorate I/R injury, we investigated the potential of bracteanolide A, from the herb Tradescantia albiflora Kunth in protecting the liver from I/R injury. We first determined the protective effect of bracteanolide A against oxidative stress and DNA damage using HepG2 hepatocyte cell line and then assessed the levels of inflammatory cytokines and antioxidant proteins in response to hepatic insult using an animal model of hepatic I/R injury. The results showed bracteanolide A greatly enhanced cell survival and decreased reactive oxygen species (ROS) production under H2O2 induction. It also upregulated the expression of nuclear factor (erythroid‐derived 2)‐like2 (Nrf2) and its downstream cytoprotective proteins NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase‐1 (HO‐1). Bracteanolide A effectively reduced the severity of liver lesions in I/R‐injured rats revealed by histological analysis and significantly decreased the levels of alanine transaminase (ALT), aspartate transaminase (AST), cyclooxygenase‐2, and inflammatory cytokines interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α. Bracteanolide A preconditioning effectively protected the liver from I/R damage in the animal model, and this easily applied procedure may provide a new means to ameliorate hepatic I/R injury during liver surgeries.
Highlights
Chronic liver disease affects millions of people and its complications, including cirrhosis and hepatocellular carcinoma, account for 3.5% of all deaths worldwide (Asrani et al, 2019; Moon et al, 2019)
To investigate the underlying reason for bracteanolide A’s protection against H2O2-induced oxidative stress and reactive oxygen species (ROS) production, we looked into changes of nuclear factor (erythroid-derived 2)-like2 (Nrf2), a key regulator in the cellular antioxidant response
NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) are transcriptional targets of Nrf2; we examined the changes in NQO1 and HO-1 expression under bracteanolide A treatment
Summary
Chronic liver disease affects millions of people and its complications, including cirrhosis and hepatocellular carcinoma, account for 3.5% of all deaths worldwide (Asrani et al, 2019; Moon et al, 2019). The end stage of chronic liver diseases calls for liver transplantation as a way to extend the patient's life. Liver ischemia and reperfusion injury (I/R injury) is a pathophysiological condition that occurs during and after liver resection, liver transplantation, and other surgical procedures involving the liver (Cannistrà et al, 2016). I/R injury is responsible for significant morbidity and mortality resulting from liver graft failure and multiple organ dysfunctions (Cannistrà et al, 2016). The two stages of an I/R injury, ischemia and reperfusion, affect different cells and tissues. When blood and oxygen supply is re-established during reperfusion, the sequential activation of CD4+ T lymphocytes, Kupffer cells, and neutrophils releases reactive oxygen species (ROS) and inflammatory cytokines such as tumor necrosis factor-a lpha (TNF-α), interleukin-1 (IL-1), and platelet-activating factor (Konishi & Lentsch, 2017)
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